Behavioral Genetics:  Research Article

Behavioral Genetics Menu

Predisposing to Social Phobia

CITATION:  Gelernter, Joel,  Page, GP, et al.  (2004).  Genome-Wide Linkage Scan for Loci Predisposing to Social Phobia: Evidence for a Chromosome 16 Risk Locus.  The American Journal of Psychiatry. Washington: Jan 2004.Vol.161, Iss. 1;  pg. 59, 8 pgs

ABSTRACT:  Social phobia is a common, sometimes disabling, fear of situations that might entail scrutiny by others. Several anxiety disorders, including social phobia, are genetically influenced. The gene encoding the norepinephrine transporter protein (SLC6A2) maps to the broad region, making SLC6A2 both a positional and physiological candidate for influencing social phobia risk.


1. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen H-U, Kendler KS; Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51:8-19

2. Gelernter CS, Uhde TW, Cimbolic P, Arnkoff DB, Vittone BJ, Tancer ME, Bartko JJ: Cognitive-behavioral and pharmacological treatments of social phobia: a controlled study. Arch Gen Psychiatry 1991; 48:938-945

3. Schneier FR, Johnson J, Hornig CD, Liebowitz MR, Weissman MM: Social phobia: comorbidity and morbidity in an epidemiologic sample. Arch Gen Psychiatry 1992; 49:282-288

4. Stein MB, Kean YM: Disability and quality of life in social phobia: epidemiologic findings. Am J Psychiatry 2000; 157:1606-1613

5. Magee W, Eaton WW, Wittchen H-U, McGonagle KA, Kessler RC: Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry 1996; 53:159-168

6. Mannuzza S, Schneier FR, Chapman TF, Liebowitz MR, Klein DF, Fyer AJ: Generalized social phobia: reliability and validity. Arch Gen Psychiatry 1995; 52:230-237

7. Nelson EC, Grant JD, Bucholz KK, Glowinski A, Madden PAF, Reich W, Heath AC: Social phobia in a population-based female adolescent twin sample: co-morbidity and associated suicide-related symptoms. Psychol Med 2000; 30:797-804

8. Stein MB, Chartier MJ, Hazen AL, Kozak MV, Tancer ME, Lander S, Furer P, Chubaty D, Walker JR: A direct-interview family study of generalized social phobia. Am J Psychiatry 1998; 155:90-97

9. Mancini C, van Ameringen M, Szatmari P, Fugere C, Boyle MA: A high-risk pilot study of the children of adults with social phobia. J Am Acad Child Adolesc Psychiatry 1996; 35:1511-1517

10. Stein MB, Chartier MJ, Lizak MV, Jang KL: Familial aggregation of anxiety-related quantitative traits in generalized social phobia: clues to understanding “disorder” heritability? Am J Med Genet 2001; 105:79-83

11. Stein MB, Torgrud LJ, Walker JR: Social phobia symptoms, subtypes and severity: findings from a community survey. Arch Gen Psychiatry 2000; 57:1046-1052

12. Fyer AJ, Mannuzza S, Chapman TF, Martin LY, Klein DF: Specificity in familial aggregation of phobic disorders. Arch Gen Psychiatry 1995; 52:564-573

13. Hettema JM, Neale MC, Kendler KS: A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 2001; 158:1568-1578

14. Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ: The genetic epidemiology of phobias in women: the interrelationship of agoraphobia, social phobia, situational phobia, and simple phobia. Arch Gen Psychiatry 1992; 49:273-281

15. Skre I, Onstad S, Torgersen S, Lygren S, Kringlen E: A twin study of DSM-III-R anxiety disorders. Acta Psychiatr Scand 1993; 88: 85-92

16. Torgersen S: Genetic factors in anxiety disorders. Arch Gen Psychiatry 1983; 40:1085-1089

17. Kendler KS, Karkowski LM, Prescott CA: Fears and phobias: reliability and heritability. Psychol Med 1999; 29:539-553

18. Kendler KS, Myers J, Prescott CA, Neale MC: The genetic epidemiology of irrational fears and phobias in men. Arch Gen Psychiatry 2001; 58:257-265

19. Stein MB, Jang KL, Livesley WJ: Heritability of social anxiety-related concerns and personality characteristics: a twin study. J Nerv Ment Dis 2002; 190:219-224

20. Stein MB, Chartier MJ, Kozak MV, King N, Kennedy JL: Genetic linkage to the serotonin transporter protein and 5HT2A receptor genes excluded in generalized social phobia. Psychiatry Res 1998; 81:283-291

21. Kennedy JL, Neves-Pereira M, King N, Lizak MV, Basile VS, Chartier MJ, Stein MB: Dopamine system genes not linked to social phobia. Psychiatr Genet 2001; 11:213-217

22. Gratacos M, Nadal M, Martin-Santos R, Pujana MA, Gago J, Peral B, Armengol L, Ponsa I, Miro R, Bulbena A, Estivill X: A polymorphic genomic duplication on human chromosome 15 is a susceptibility factor for panic and phobic disorders. Cell 2001; 106:367-379

23. Gelernter J, Bonvicini K, Page G, Woods SW, Goddard AW, Kruger S, Pauls DL, Goodson S: Linkage genome scan for loci predisposing to panic disorder or agoraphobia. Am J Med Genet Neuropsychiatr Genet 2001; 105:548-557

24. Gelernter J, Page G, Bonvicini K, Woods SW, Pauls DL, Kruger S: A chromosome 14 risk locus for simple phobia: results from a genomewide linkage scan. Mol Psychiatry 2003; 8:71-82

25. Spitzer RL, Endicott J: Schedule for Affective Disorders and Schizophrenia-Lifetime Version. New York, New York State Psychiatric Institute, Biometrics Research, 1975

26. First MB, Spitzer RL, Gibbon M, Williams JBW: Structured Clinical Interview for DSM-IV Axis I Disorders Research Version, Non-Patient Edition (SCID-NP), version 2. New York, New York State Psychiatric Institute, Biometrics Research, 1997

27. Boehnke M: Estimating the power of a proposed linkage study: a practical computer simulation approach. Am J Hum Genet 1986; 39:513-527

28. Broman KW, Murray JC, Sheffield VC, White RL, Weber JL: Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genetics 1998; 63:861-869

29. O’Connell JR, Weeks DE: PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 1998; 63:259-266

30. McPeek MS, Sun L: Statistical tests for detection of misspecified relationships by use of genome-screen data. Am J Hum Genet 2000; 66:1076-1094

31. Gudbjartsson DF, Jonasson K, Frigge ML, Kong A: Allegro, a new computer program for multipoint linkage analysis (letter). Nat Genet 2000; 25:12-13

32. Knowles JA, Fyer AJ, Vieland VJ, Weissman MM, Hodge SE, Heiman GA, Haghighi F, de Jesus GM, Rassnick H, Preud’homme-Rivelli X, Austin T, Cunjak J, Mick S, Fine LD, Woodley KA, Das K, Maier W, Adams PB, Freimer NB, Klein DF, Gilliam TC: Results of a genome-wide genetic screen for panic disorder. Am J Med Genet Neuropsychiatr Genet 1998; 81:139-147

33. Kong A, Cox NJ: Allele-sharing models: LOD scores and accurate linkage tests. Am J Hum Genet 1997; 61:1179-1188

34. Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES: Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet 1996; 58:1347-1363

35. Xu J, Meyers DA, Pericak-Vance MA: Lod score analysis, in Approaches to Gene Mapping in Complex Human Diseases. Edited by Haines JL, Pericak-Vance MA. New York, Wiley-Liss, 1998, pp 253-272

36. Clerget-Darpoux F, Bonaiti-Pellie C, Hochez J: Effects of misspecifying genetic parameters in lod score analysis. Biometrics 1986; 42:393-399

37. Lander E, Kruglyak L: Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Gen 1995; 11:241-247

38. Gorman JM, Kent JM: SSRIs and SNRIs: broad spectrum of efficacy beyond major depression. J Clin Psychiatry 2002; 60(suppl 4):33-38

39. Owens MJ, Knight D, Nemeroff CB: Paroxetine binding to the rat norepinephrine transporter in vivo. Biol Psychiatry 2000; 47:842-845

40. Tiihonen J, Kuikka J, Bergstrom K, Lepola U, Koponen H, Leinonen E: Dopamine reuptake site densities in patients with social phobia. Am J Psychiatry 1997; 154:239-242

41. Gelernter J, Kruger S, Pakstis AJ, Pacholczyk T, Sparkes RS, Kidd KK, Amara S: Assignment of the norepinephrine transporter protein (NET1) locus to chromosome 16. Genomics 1993; 18: 690-692

42. Kendler KS, Walters EE, Neale MC, Kessler RC, Heath AC, Eaves LJ: The structure of the genetic and environmental risk factors for six major psychiatric disorders in women: phobia, generalized anxiety disorder, panic disorder, bulimia, major depression, and alcoholism. Arch Gen Psychiatry 1995; 52:374-383